# Philadelphia chromosome-positive de novo myelodysplastic syndrome with the p230 BCR::ABL1 fusion gene: a case report

## TL;DR

A rare case of myelodysplastic syndrome with a specific BCR::ABL1 fusion gene is reported, showing mixed treatment responses and the importance of genomic analysis.

## Contribution

This case report highlights the clinical and genomic complexity of Ph-positive MDS with p230 BCR::ABL1 and the role of NGS in therapeutic decision-making.

## Key findings

- Low-dose dasatinib reduced BCR::ABL1 levels but did not improve anemia or dysplasia.
- Ph positivity emerged as a late event on an ASXL1-mutant background.
- Persistence of the ASXL1 founder clone suggests limited treatment efficacy despite BCR::ABL1 clearance.

## Abstract

De novo Ph-positive MDS with the micro BCR::ABL1 (e19a2/p230) transcript is rare. Here, we report a case of MDS with multilineage dysplasia in an 86-year-old woman. Reverse transcription polymerase chain reaction (RT-PCR) showed the following karyotype: 46, XX, t(9;22)(q34.1;q11.2), i(17)(q10) [20], and p230 BCR::ABL1. Targeted NGS at diagnosis revealed mutations in CSF3R, BCOR, SRSF2, and ASXL1. Low-dose dasatinib (20 mg/day) reduced BCR::ABL1 levels (FISH negative, RT-PCR positive), but had no effect on anemia, dysplasia, or transfusion frequency. At six months, panel results showed loss of all mutations except ASXL1, as well as clearance of Ph-positive subclones. However, an ASXL1 founder clone persisted. Post-treatment chromosome analysis was not feasible because of poor cell growth. Serial genomics suggested that Ph positivity was a late/secondary event on a pre-existing ASXL1-mutant background. In Ph-positive de novo MDS, BCR::ABL1 transcript responses alone may not reflect disease control when an adverse founder clone persists. Integrating panel-based NGS with fusion transcript monitoring may improve therapeutic decision-making and prognostic assessment.